RESUMO
Objective: This study aims to examine the frequency of Salmonella Paratyphi found in blood cultures and evaluate the antibiotic susceptibility pattern of Salmonella isolates to different antibiotics. Additionally, the study aims to assess the paradigm shift in the trend of enteric fever caused by Salmonella Typhi (S. Typhi) to Salmonella Paratyphi(S. Paratyphi) . Study Design: Retrospective study. Participant: The study enrolled patients aged 12 years and above diagnosed with enteric fever (positive blood culture) and admitted to Peelamedu Samanaidu Govindasamy Naidu (PSG) Hospital. Interventions: The study analyzed demographic and antibiotic susceptibility profiles of Salmonella isolates collected from 106 enteric fever patients in the hospital between 2010 and 2022. The susceptibility profiles of Salmonella isolates to multiple antibiotics were assessed. Results: There were 106 participants, and 95 (89.62%) of them had enteric fever linked to Salmonella Typhi, while only 11 (10.38%) had enteric fever linked to Salmonella Paratyphi A. From 2010 to 2022, the study discovered a general decline in the prevalence of enteric fever caused by Salmonella species. But between 2014 and 2022, the incidence of enteric fever linked to S. Typhi rapidly increased. Azithromycin (100% , n = 106) and ceftriaxone (99% , n = 105) were highly effective against the Salmonella isolates, whereas nalidixic acid was resisted by 3 isolates (4.72%, n = 3). Conclusion: The study observed a higher incidence of Salmonella Typhi in comparison to Paratyphi A and a greater susceptibility of males to enteric fever. Funding: None declared.
Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Salmonella paratyphi A , Salmonella typhi , Febre Tifoide , Humanos , Masculino , Feminino , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Febre Tifoide/epidemiologia , Febre Tifoide/microbiologia , Febre Tifoide/tratamento farmacológico , Estudos Retrospectivos , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/isolamento & purificação , Salmonella paratyphi A/efeitos dos fármacos , Salmonella paratyphi A/isolamento & purificação , Adulto , Adolescente , Criança , Pessoa de Meia-Idade , Adulto Jovem , Febre Paratifoide/epidemiologia , Febre Paratifoide/microbiologia , Febre Paratifoide/tratamento farmacológico , Incidência , Farmacorresistência Bacteriana , Azitromicina/uso terapêutico , Azitromicina/farmacologia , Ceftriaxona/uso terapêutico , Ceftriaxona/farmacologia , Idoso , PrevalênciaRESUMO
Salmonella Paratyphi A, one of the major etiologic agents of enteric fever, has increased in prevalence in recent decades in certain endemic regions in comparison to S. Typhi, the most prevalent cause of enteric fever. Despite this increase, data on the prevalence and molecular epidemiology of S. Paratyphi A remain generally scarce. Here, we analysed the whole genome sequences of 216 S. Paratyphi A isolates originating from Kathmandu, Nepal between 2005 and 2014, of which 200 were from patients with acute enteric fever and 16 from the gallbladder of people with suspected chronic carriage. By exploiting the recently developed genotyping framework for S. Paratyphi A (Paratype), we identified several genotypes circulating in Kathmandu. Notably, we observed an unusual clonal expansion of genotype 2.4.3 over a four-year period that spread geographically and systematically replaced other genotypes. This rapid genotype replacement is hypothesised to have been driven by both reduced susceptibility to fluoroquinolones and genetic changes to virulence factors, such as functional and structural genes encoding the type 3 secretion systems. Finally, we show that person-to-person is likely the most common mode of transmission and chronic carriers seem to play a limited role in maintaining disease circulation.
Assuntos
Genótipo , Febre Paratifoide , Salmonella paratyphi A , Nepal/epidemiologia , Humanos , Salmonella paratyphi A/genética , Salmonella paratyphi A/isolamento & purificação , Salmonella paratyphi A/classificação , Estudos Retrospectivos , Febre Paratifoide/epidemiologia , Febre Paratifoide/microbiologia , Masculino , Adulto , Feminino , Adulto Jovem , Adolescente , Criança , Prevalência , Pessoa de Meia-Idade , Epidemiologia Molecular , Pré-Escolar , Sequenciamento Completo do Genoma , Antibacterianos/farmacologia , FilogeniaRESUMO
BACKGROUND: The proportion of enteric fever cases caused by Salmonella Paratyphi A is increasing and may increase further as we begin to introduce typhoid conjugate vaccines (TCVs). While numerous epidemiological and genomic studies have been conducted for S. Typhi, there are limited data describing the genomic epidemiology of S. Paratyphi A in especially in endemic settings, such as Bangladesh. PRINCIPAL FINDINGS: We conducted whole genome sequencing (WGS) of 67 S. Paratyphi A isolated between 2008 and 2018 from eight enteric disease surveillance sites across Bangladesh. We performed a detailed phylogenetic analysis of these sequence data incorporating sequences from 242 previously sequenced S. Paratyphi A isolates from a global collection and provided evidence of lineage migration from neighboring countries in South Asia. The data revealed that the majority of the Bangladeshi S. Paratyphi A isolates belonged to the dominant global lineage A (67.2%), while the remainder were either lineage C (19.4%) or F (13.4%). The population structure was relatively homogenous across the country as we did not find any significant lineage distributions between study sites inside or outside Dhaka. Our genomic data showed presence of single point mutations in gyrA gene either at codon 83 or 87 associated with decreased fluoroquinolone susceptibility in all Bangladeshi S. Paratyphi A isolates. Notably, we identified the pHCM2- like cryptic plasmid which was highly similar to S. Typhi plasmids circulating in Bangladesh and has not been previously identified in S. Paratyphi A organisms. SIGNIFICANCE: This study demonstrates the utility of WGS to monitor the ongoing evolution of this emerging enteric pathogen. Novel insights into the genetic structure of S. Paratyphi A will aid the understanding of both regional and global circulation patterns of this emerging pathogen and provide a framework for future genomic surveillance studies.
Assuntos
Salmonella paratyphi A/genética , Febre Tifoide/microbiologia , Proteínas de Bactérias/genética , Bangladesh/epidemiologia , Pré-Escolar , Feminino , Variação Genética , Humanos , Lactente , Masculino , Filogenia , Mutação Puntual , Polimorfismo de Nucleotídeo Único , Salmonella paratyphi A/classificação , Salmonella paratyphi A/isolamento & purificação , Febre Tifoide/epidemiologia , Sequenciamento Completo do GenomaAssuntos
Abscesso Abdominal/microbiologia , Rim , Febre Paratifoide/diagnóstico , Doença Relacionada a Viagens , Adulto , Sudeste Asiático , Humanos , Rim/microbiologia , Rim/patologia , Masculino , Febre Paratifoide/complicações , Infecções por Salmonella/diagnóstico , Salmonella paratyphi A/isolamento & purificação , Febre Tifoide/complicações , Febre Tifoide/diagnóstico , Infecções Urinárias/diagnóstico , Infecções Urinárias/microbiologiaRESUMO
INTRODUCTION: With increasing fluoroquinolone resistance, extended spectrum cephalosporins are recommended for the treatment of invasive Salmonella infections. However, Extended spectrum beta-lactamases (ESBL) producing Salmonella Paratyphi A causing enteric fever is on the rise and constitutes a major therapeutic challenge. Hence, we aimed to assess the incidence of ESBL production, fluoroquinolone resistance in S. Paratyphi A and to compare the fluoroquinolone resistance detection methods. METHODOLOGY: Seventeen blood-culture isolates of S. Paratyphi A were tested for susceptibility to ampicillin, chloramphenicol, co-trimoxazole, streptomycin and tetracycline (ACCuST), fluoroquinolones, azithromycin and ceftriaxone by disk diffusion method. We compared and correlated between disk diffusion of ciprofloxacin and pefloxacin with ciprofloxacin MIC. Combined disk test was employed to determine ESBL production. RESULTS: In this study, 13(76.5%) isolates were nalidixic acid resistant (NAR), 16 (94.1%) were pefloxacin resistant, while 7 (41.2%), 9 (52.9%) exhibited resistance and intermediate susceptibility to ciprofloxacin respectively. The MIC50, MIC90 of ciprofloxacin was 1 µg/mL, 2 µg/mL respectively. Among the NAR, 76.92% were DSC (MIC 0.5-1 µg/mL) and 23.08% had an MIC of 2-4 µg/mL. Of note, 4 isolates with DSC were NAS. Of the 17 S. Paratyphi A isolates, 14 (82.4%) were ESBL producers and 11 (64.7%) isolates were ceftriaxone susceptible. CONCLUSIONS: Multidrug resistant (AmpRChlRSxtR) S. Paratyphi A with combined resistance to fluoroquinolones and ESBL production is a cause of concern. We found S. Paratyphi A isolates with a relatively unusual phenotype: nalidixic acid susceptible but exhibited DSC; pefloxacin susceptible but ciprofloxacin resistant. Of note one multidrug resistant (AmpRChlRSxtR) isolate, an ESBL producer exhibited resistance to azithromycin, cephalosporins and fluoroquinolones but was susceptible to carbapenems and streptomycin.
Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Fluoroquinolonas/uso terapêutico , Ácido Nalidíxico/uso terapêutico , Febre Tifoide/microbiologia , Antibacterianos/farmacologia , Fluoroquinolonas/farmacologia , Humanos , Índia , Testes de Sensibilidade Microbiana , Ácido Nalidíxico/farmacologia , Salmonella paratyphi A/isolamento & purificação , Febre Tifoide/tratamento farmacológicoRESUMO
Diseases caused by typhoidal and non-typhoidal Salmonella remain a considerable threat to both developed and developing countries. Based on the clinical symptoms and serological tests, it is sometimes difficult to differentiate the Salmonella enterica serovar Paratyphi A (S. enterica serovar Paratyphi A) from serovar Typhi (S. enterica serovar Typhi). In this study, we developed a quadruplex real-time polymerase chain reaction (PCR) assay with an internal amplification control (IAC), to simultaneously differentiate S. enterica serovar Paratyphi A from serovar Typhi and to detect other Salmonella serovars which cause salmonellosis in humans. This assay was evaluated on 155 salmonellae and non-salmonellae strains and demonstrated 100% specificity in species differentiation. Inclusion of an IAC did not affect the efficiency of the assay. Further evaluation using a blind test on spiked stool, blood and food specimens showed that the detection limit was at 103 -104 CFU/mL (or g) and a high PCR efficiency with different targets (R2 > 0.99), except for S. enterica serovar Paratyphi A in blood. This assay has been applied to clinical specimens to detect the causative agents of gastrointestinal infections and has successfully identified 6 salmonellosis patients from the 50 diarrhoea patients. The quadruplex real-time PCR developed in this study could enhance the detection and differentiation of salmonellae. This assay could be applied to stools, blood and food based on the notable performance in the simulation tests and field evaluation.
Assuntos
Técnicas de Tipagem Bacteriana/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Infecções por Salmonella/diagnóstico , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/isolamento & purificação , Fezes/microbiologia , Humanos , Infecções por Salmonella/sangue , Salmonella paratyphi A/genética , Salmonella typhi/genéticaAssuntos
Antibacterianos/uso terapêutico , Febre Paratifoide/diagnóstico , Polissacarídeos Bacterianos/administração & dosagem , Doença Relacionada a Viagens , Febre Tifoide/diagnóstico , Vacinas Tíficas-Paratíficas/administração & dosagem , Antibacterianos/farmacologia , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Dengue/diagnóstico , Diagnóstico Diferencial , Doxiciclina/farmacologia , Doxiciclina/uso terapêutico , Farmacorresistência Bacteriana , Doenças Endêmicas , Humanos , Malária/diagnóstico , Febre Paratifoide/tratamento farmacológico , Febre Paratifoide/microbiologia , Febre Paratifoide/prevenção & controle , Salmonella paratyphi A/efeitos dos fármacos , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/isolamento & purificação , Febre Tifoide/tratamento farmacológico , Febre Tifoide/microbiologia , Febre Tifoide/prevenção & controleRESUMO
OBJECTIVES: Enteric fever remains an important diagnostic and treatment challenge in febrile children living in the tropics. In the context of a national Salmonella enterica serovar Paratyphi A outbreak, the objective of this retrospective study was to compare features of S. Typhi and S. Paratyphi A infections in Cambodian children. METHODS: Clinical and laboratory features were reviewed for 192 blood culture-confirmed children with S. Typhi and S. Paratyphi A infections presenting to a paediatric referral hospital in Siem Reap, 2012-2016. RESULTS: Children with S. Typhi infections were younger, were more likely to have chills and/or diarrhoea, and were more frequently hospitalized than those with S. Paratyphi A infections. Over three quarters (88.3%) of S. Typhi isolates were multidrug-resistant, compared to none of the S. Paratyphi A. CONCLUSIONS: In this small study of Cambodian children, S. Typhi infections were more severe than S. Paratyphi A infections. Antibiotic resistance limits treatment options for enteric fever in this population.
Assuntos
Febre Paratifoide/microbiologia , Salmonella paratyphi A/fisiologia , Salmonella typhi/fisiologia , Febre Tifoide/microbiologia , Adolescente , Antibacterianos/administração & dosagem , Camboja/epidemiologia , Criança , Pré-Escolar , Feminino , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Lactente , Masculino , Febre Paratifoide/tratamento farmacológico , Febre Paratifoide/epidemiologia , Estudos Retrospectivos , Salmonella paratyphi A/genética , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/genética , Salmonella typhi/isolamento & purificação , Febre Tifoide/tratamento farmacológico , Febre Tifoide/epidemiologiaRESUMO
Introduction. Identification of typhoidal Salmonella (TS) serovars and their discrimination from non-typhoidal Salmonella (NTS) is conventionally performed by seroagglutination. This method is labour-intensive, requires technical experience and can be inconclusive in some cases. Molecular assays may be reliable alternative diagnostic tools.Aim. This study was designed to evaluate the eazyplex TyphiTyper based on loop-mediated isothermal amplification (LAMP) for fast identification of TS and S. Choleraesuis in culture.Methodology. A total of 121 Salmonella strains and 33 isolates of other Enterobacterales species were tested by the eazyplex TyphiTyper. Simulated and clinical blood cultures (BCs) were used to examine the performance of the assay for diagnosis of systemic infection. Sample preparation took about 5 min and the test running time was 20 min. Amplification was measured by real-time fluorescence detection.Results. All TS and S. Choleraesuis strains were correctly identified. The most common NTS S. Typhimurium (n=34) and S. Enteritidis (n=15) were detected as Salmonella species without any false positive result for TS targets. Cross-reactions of NTS with TS were only rarely observed. Direct testing of positive BCs gave correct results. Sensitivities and specificities of the assay were as follows: 100 and 99.3â% for S. Typhi, 100 and 98.7â% for S. Paratyphi A, 100 and 97.3â% for S. Paratyphi B, 100 and 100â% for S. Paratyphi C, 100 and 100â% for S. Choleraesuis, and 100 and 100â% for Salmonella species, respectively.Conclusion. The eazyplex TyphiTyper is very easy to perform and allows the rapid identification of TS and S. Choleraesuis isolates.
Assuntos
Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Salmonella/isolamento & purificação , Humanos , Salmonella/classificação , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/isolamento & purificaçãoRESUMO
Typhoid fever and paratyphoid fever are systemic infectious diseases of global significance caused by Salmonella enterica subspecies enterica Serovar Typhi (short name: Salmonella Typhi) or Serovar Paratyphi (short name: Salmonella Paratyphi). The course of these fecal-orally transmitted diseases is mainly characterized by a high fever. Left untreated, the course of typhoid fever can be severe and lethal. The infection is almost always acquired outside of Europe (mainly in India) and is notifiable in Germany, Austria and Switzerland. Paratyphoid is an attenuated disease of typhoid fever caused by Salmonella Paratyphi. Available vaccines only protect against Salmonella Typhi. Antibiotic resistance reflects the situation in endemic countries and shows a worrying increase of multi-drug resistant isolates. Currently, third-generation cephalosporins such as ceftriaxone are recommended as first-line therapy; if sensitive to quinolones, fluoroquinolones such as ciprofloxacin may continue to be administered. Crucial preventive measures for travelers to endemic regions include consistent water and food hygiene as well as vaccination, whereby only protection rates of 50-70â% are achieved by currently available vaccines. In the light of increasing multi-drug resistance, a more effective conjugate vaccine against Salmonella Typhi with cross-reactivity against Salmonella Paratyphi is needed more than ever.
Assuntos
Antibacterianos/farmacologia , Febre Paratifoide/tratamento farmacológico , Febre Paratifoide/prevenção & controle , Salmonella paratyphi A/efeitos dos fármacos , Salmonella typhi/efeitos dos fármacos , Febre Tifoide/tratamento farmacológico , Febre Tifoide/prevenção & controle , Vacinas Conjugadas/administração & dosagem , Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Fluoroquinolonas/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Febre Paratifoide/diagnóstico , Febre Paratifoide/microbiologia , Quinolonas/uso terapêutico , Salmonella enterica , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/isolamento & purificação , Febre Tifoide/diagnóstico , Febre Tifoide/microbiologiaRESUMO
BACKGROUND: Antimicrobial resistance (AMR) is an increasing threat to global health. There are > 14 million cases of enteric fever every year and > 135,000 deaths. The disease is primarily controlled by antimicrobial treatment, but this is becoming increasingly difficult due to AMR. Our objectives were to assess the prevalence and geographic distribution of AMR in Salmonella enterica serovars Typhi and Paratyphi A infections globally, to evaluate the extent of the problem, and to facilitate the creation of geospatial maps of AMR prevalence to help targeted public health intervention. METHODS: We performed a systematic review of the literature by searching seven databases for studies published between 1990 and 2018. We recategorised isolates to allow the analysis of fluoroquinolone resistance trends over the study period. The prevalence of multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) in individual studies was illustrated by forest plots, and a random effects meta-analysis was performed, stratified by Global Burden of Disease (GBD) region and 5-year time period. Heterogeneity was assessed using the I2 statistics. We present a descriptive analysis of ceftriaxone and azithromycin resistance. FINDINGS: We identified 4557 articles, of which 384, comprising 124,347 isolates (94,616 S. Typhi and 29,731 S. Paratyphi A) met the pre-specified inclusion criteria. The majority (276/384; 72%) of studies were from South Asia; 40 (10%) articles were identified from Sub-Saharan Africa. With the exception of MDR S. Typhi in South Asia, which declined between 1990 and 2018, and MDR S. Paratyphi A, which remained at low levels, resistance trends worsened for all antimicrobials in all regions. We identified several data gaps in Africa and the Middle East. Incomplete reporting of antimicrobial susceptibility testing (AST) and lack of quality assurance were identified. INTERPRETATION: Drug-resistant enteric fever is widespread in low- and middle-income countries, and the situation is worsening. It is essential that public health and clinical measures, which include improvements in water quality and sanitation, the deployment of S. Typhi vaccination, and an informed choice of treatment are implemented. However, there is no licenced vaccine for S. Paratyphi A. The standardised reporting of AST data and rollout of external quality control assessment are urgently needed to facilitate evidence-based policy and practice. TRIAL REGISTRATION: PROSPERO CRD42018029432.
Assuntos
Salmonella paratyphi A , Salmonella typhi , Febre Tifoide/epidemiologia , Antibacterianos/farmacologia , Azitromicina/farmacologia , Farmacorresistência Bacteriana , Saúde Global , Humanos , Febre Paratifoide/epidemiologia , Prevalência , Salmonella paratyphi A/classificação , Salmonella paratyphi A/efeitos dos fármacos , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/classificação , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/isolamento & purificação , Febre Tifoide/tratamento farmacológicoRESUMO
Chronically infected diabetic wounds have a polymicrobial aetiology. However, Salmonella Paratyphi A is a very rare cause of wound infection. A 76-year-old female patient with type II diabetes presented with a wound on the left leg of two months' duration. The wound was painful, erythematous and a thick, foul-smelling discharge was present. There was a history of delayed wound healing. Salmonella Paratyphi A and Pseudomonas aeruginosa were isolated from the wound tissue. The patient was treated with cefuroxime and cloxacillin empirically and following the antibiotic susceptibility testing (ABST) report, ciprofloxacin was given for 10 days. The wound was treated with multiple debridements and topical antiseptic. On follow-up, the patient remained afebrile with subsiding discharge from the ulcer. This is the first reported case of Salmonella Paratyphi A from an infected diabetic ulcer in Sri Lanka and it serves to further define the spectrum of illnesses caused by this uncommon pathogen.
Assuntos
Antibacterianos/administração & dosagem , Ciprofloxacina/administração & dosagem , Diabetes Mellitus Tipo 2/complicações , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Úlcera da Perna/microbiologia , Salmonella paratyphi A/isolamento & purificação , Idoso , Anti-Infecciosos Locais/administração & dosagem , Cefuroxima/administração & dosagem , Cloxacilina/administração & dosagem , Desbridamento , Feminino , Infecções por Bactérias Gram-Negativas/etiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Úlcera da Perna/etiologia , Úlcera da Perna/fisiopatologia , Testes de Sensibilidade Microbiana , Febre Paratifoide/tratamento farmacológico , Febre Paratifoide/etiologia , Febre Paratifoide/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/etiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Salmonella paratyphi A/efeitos dos fármacos , CicatrizaçãoRESUMO
BACKGROUND: In surveillance for typhoid fever, under-detection of cases occurs when patients with fever do not seek medical care, or seek medical care but do not receive a blood test. Missing data may result in incorrect estimates of disease incidence. METHODS: We used data from an ongoing randomised clinical trial of typhoid conjugate vaccine among children in Nepal to determine if eligible patients attending our fever clinics who did not have blood taken for culture had a lower risk of disease than those who had blood drawn. We assessed clinical and demographic predictors of having blood taken for culture, and predictors of culture-positive results. Missing blood culture data were imputed using multiple imputations. RESULTS: During the first year of surveillance, 2392 fever presentations were recorded and 1615 (68%) of these had blood cultures. Children were more likely to have blood taken for culture if they were older, had fever for longer, a current temperature ≥38 degrees, or if typhoid or a urinary tract infection were suspected. Based on imputation models, those with blood cultures were 1.87 times more likely to have blood culture-positive fever than those with missing data. CONCLUSION: Clinical opinion on the cause of the fever may play a large part in the decision to offer blood culture, regardless of study protocol. Crude typhoid incidence estimates should be adjusted for the proportion of cases that go undetected due to missing blood cultures while adjusting for the lower likelihood of culture-positivity in the group with missing data.
Assuntos
Hemocultura/estatística & dados numéricos , Febre/diagnóstico , Febre Tifoide/diagnóstico , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Masculino , Diagnóstico Ausente , Nepal/epidemiologia , Febre Paratifoide/sangue , Febre Paratifoide/diagnóstico , Febre Paratifoide/epidemiologia , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/isolamento & purificação , Febre Tifoide/sangue , Febre Tifoide/epidemiologia , Infecções UrináriasRESUMO
Whole genome sequencing (WGS) has been used routinely by Public Health England (PHE) for identification, surveillance and monitoring of resistance determinants in referred Salmonella isolates since 2015. We report the first identified case of extended-spectrum-ß-lactamase (ESBL) Salmonella enterica serovar Paratyphi A (S. Paratyphi A) isolated from a traveller returning to England from Bangladesh in November 2017. The isolate (440915) was resistant to ciprofloxacin and harboured both the mobile element ISEcp9 -blaCTX-M-15-hp-tnpA and blaTEM-191, associated with ESBL production. Phenotypic resistance was subsequently confirmed by Antimicrobial Susceptibility Testing (AST). S. Paratyphi A 440915 harboured an IncI1 plasmid previously reported to encode ESBL elements in Enterobacteriaceae and recently described in a S. Typhi isolate from Bangladesh. Results from this study indicate the importance of monitoring imported drug resistance for typhoidal salmonellae as ceftriaxone is the first line antibiotic treatment for complicated enteric fever in England. We conclude that WGS provides a rapid, accurate method for surveillance of drug resistance genes in Salmonella, leading to the first reported case of ESBL producing S. Paratyphi A and continues to inform the national treatment guidelines for management of enteric fever.
Assuntos
Febre Paratifoide/diagnóstico , Fatores R , Salmonella paratyphi A/genética , Salmonella paratyphi A/isolamento & purificação , Viagem , Adulto , Bangladesh , DNA Bacteriano , Inglaterra , Humanos , Masculino , Febre Paratifoide/microbiologia , Salmonella paratyphi A/efeitos dos fármacos , Sequenciamento Completo do Genoma , Resistência beta-Lactâmica/genéticaRESUMO
In Mexico, information of Salmonella enterica cases linked to food consumption is scarce. The objective of this article was to assess how S. enterica affect public health in Mexico. To conduct this study, data on the epidemiology of nontyphoidal S. enterica (NTS), Salmonella Typhi, and Salmonella Paratyphi A collected from 2000 to 2017 through the National Epidemiological Surveillance System of Mexico (Sistema Nacional de Vigilancia Epidemiológica de Mexico [SINAVE]) were used. Geographical distribution, season, age groups, and gender were variables considered to analyze S. enterica incidence. An estimation of cases caused by S. enterica in Mexico was calculated while considering data underestimation and the proportion of foodborne diseases. Information of the prevalence of the pathogen in food and the antimicrobial resistance of isolates from food and human cases were obtained from published studies. Outbreaks of S. enterica derived from imported Mexican products in the Unites States are discussed. In 2017, the numbers of reported cases of NTS (92,013) were two and seven times higher than the reported cases of Salmonella Typhi (45,280) and Salmonella Paratyphi A (12, 458). The NTS incidence was higher in lower socioeconomic Mexican regions. The gaps in the surveillance system make it impossible to establish a reliable tendency among age groups, geographical distribution, and gender. In 2017, the estimated frequency of NTS foodborne cases was 49 times higher than that reported in SINAVE, whereas for Salmonella Typhi and Salmonella Paratyphi A it was 23 times. Fresh meat showed the highest prevalence of S. enterica, and most of their isolates had multidrug resistance. Salmonella Typhimurium was the most common serotype isolated from human cases and food. Food safety agencies in Mexico need to prioritize efforts and resources to establish guidelines to ensure the absence of S. enterica in food.
Assuntos
Doenças Transmitidas por Alimentos/epidemiologia , Infecções por Salmonella/epidemiologia , Infecções por Salmonella/microbiologia , Salmonella enterica/isolamento & purificação , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/isolamento & purificação , Farmacorresistência Bacteriana Múltipla , Inocuidade dos Alimentos , Doenças Transmitidas por Alimentos/microbiologia , Humanos , Carne/microbiologia , México/epidemiologia , Prevalência , Verduras/microbiologiaRESUMO
Enteric fever is one of the leading causes of infection and subsequent fatality (greater than 1.8 million) (WHO 2018), especially in the developing countries due to contaminated water and food inter twinned with unhygienic practices. Clinical gold standard technique of culture-based method followed by biochemical tests demand 72+ hours for diagnosis while newly developed techniques (like PCR, RT-PCR, DNA microarray etc.) suffer from high limit of detection or involve high-cost infrastructure or both. In this work, a quick and highly specific method, SMOL was established for simultaneous detection of Salmonella paratyphi A and Salmonella typhi in clinical blood samples. SMOL consists of (i) pre-concentration of S. typhi and S. paratyphi A cells using magnetic nanoparticles followed by (ii) cell lysis and DNA extraction (iii) amplification of select nucleic acids by LAMP technique and (iv) detection of amplified nucleic acids using an affordable portable device (costs less than $70). To identify the viability of target cells at lower concentrations, the samples were processed at two different time periods of t = 0 and t = 4 h. Primers specific for the SPA2539 gene in S. paratyphi A and STY2879 gene in S. typhi were used for LAMP. Within 6 h SMOL was able to detect positive and negative samples from 55 human clinical blood culture samples and detect the viability of the cells. The results were concordant with culture and biochemical tests as well as by qPCR. Statistical power analysis yielded 100%. SMOL results were concordant with culture and biochemical tests as well as by qPCR. The sensitive and affordable system SMOL will be effective for poor resource settings.
Assuntos
Sangue/microbiologia , Custos e Análise de Custo , Limite de Detecção , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/isolamento & purificação , Testes Sorológicos/economia , Testes Sorológicos/instrumentação , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Humanos , Técnicas de Amplificação de Ácido Nucleico , Salmonella paratyphi A/genética , Salmonella typhi/genética , Fatores de Tempo , Febre Tifoide/microbiologiaRESUMO
BACKGROUND: With the rise in fluoroquinolone-resistant Salmonella Typhi and the recent emergence of ceftriaxone resistance, azithromycin is one of the last oral drugs available against typhoid for which resistance is uncommon. Its increasing use, specifically in light of the ongoing outbreak of extensively drug-resistant (XDR) Salmonella Typhi (resistant to chloramphenicol, ampicillin, cotrimoxazole, streptomycin, fluoroquinolones and third-generation cephalosporins) in Pakistan, places selective pressure for the emergence and spread of azithromycin-resistant isolates. However, little is known about azithromycin resistance in Salmonella, and no molecular data are available on its mechanism. METHODS AND FINDINGS: We conducted typhoid surveillance in the two largest pediatric hospitals of Bangladesh from 2009-2016. All typhoidal Salmonella strains were screened for azithromycin resistance using disc diffusion and resistance was confirmed using E-tests. In total, we identified 1,082 Salmonella Typhi and Paratyphi A strains; among these, 13 strains (12 Typhi, 1 Paratyphi A) were azithromycin-resistant (MIC range: 32-64 µg/ml) with the first case observed in 2013. We sequenced the resistant strains, but no molecular basis of macrolide resistance was identified by the currently available antimicrobial resistance prediction tools. A whole genome SNP tree, made using RAxML, showed that the 12 Typhi resistant strains clustered together within the 4.3.1.1 sub-clade (H58 lineage 1). We found a non-synonymous single-point mutation exclusively in these 12 strains in the gene encoding AcrB, an efflux pump that removes small molecules from bacterial cells. The mutation changed the conserved amino acid arginine (R) at position 717 to a glutamine (Q). To test the role of R717Q present in azithromycin-resistant strains, we cloned acrB from azithromycin-resistant and sensitive strains, expressed them in E. coli, Typhi and Paratyphi A strains and tested their azithromycin susceptibility. Expression of AcrB-R717Q in E. coli and Typhi strains increased the minimum inhibitory concentration (MIC) for azithromycin by 11- and 3-fold respectively. The azithromycin-resistant Paratyphi A strain also contained a mutation at R717 (R717L), whose introduction in E. coli and Paratyphi A strains increased MIC by 7- and 3-fold respectively, confirming the role of R717 mutations in conferring azithromycin resistance. CONCLUSIONS: This report confirms 12 azithromycin-resistant Salmonella Typhi strains and one Paratyphi A strain. The molecular basis of this resistance is one mutation in the AcrB protein at position 717. This is the first report demonstrating the impact of this non-synonymous mutation in conferring macrolide resistance in a clinical setting. With increasing azithromycin use, strains with R717 mutations may spread and be acquired by XDR strains. An azithromycin-resistant XDR strain would shift enteric fever treatment from outpatient departments, where patients are currently treated with oral azithromycin, to inpatient departments to be treated with injectable antibiotics like carbapenems, thereby further burdening already struggling health systems in endemic regions. Moreover, with the dearth of novel antimicrobials in the horizon, we risk losing our primary defense against widespread mortality from typhoid. In addition to rolling out the WHO prequalified typhoid conjugate vaccine in endemic areas to decrease the risk of pan-resistant Salmonella Typhi strains, it is also imperative to implement antimicrobial stewardship and water sanitation and hygiene intervention to decrease the overall burden of enteric fever.
Assuntos
Antibacterianos/farmacologia , Azitromicina/farmacologia , Farmacorresistência Bacteriana , Salmonella paratyphi A/efeitos dos fármacos , Salmonella typhi/efeitos dos fármacos , Febre Tifoide/microbiologia , Proteínas de Bactérias , Bangladesh , DNA Bacteriano/química , DNA Bacteriano/genética , Genótipo , Hospitais Pediátricos , Humanos , Proteínas de Membrana Transportadoras , Testes de Sensibilidade Microbiana , Polimorfismo de Nucleotídeo Único , Salmonella paratyphi A/classificação , Salmonella paratyphi A/genética , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/classificação , Salmonella typhi/genética , Salmonella typhi/isolamento & purificação , Sequenciamento Completo do GenomaRESUMO
Salmonella infections in poultry farms are overlooked in many African countries; yet these infections are mostly zoonotic with impact on both poultry industry and public health. Considering the impact of Salmonella in laying hens, and the role of laying hens as a source of Salmonella outbreak in human, knowledge of the status of Salmonella on laying hen farms as well as the factors influencing the presence of Salmonella is important. In a cross sectional study, cloacal swabs were collected from 270 commercial laying hens on 27 farms located in Menoua Division. These samples were cultured on standard media. A questionnaire was used to collect information on animals, farms and farmer's characteristics. The prevalence of Salmonella was 93.34%; three zoonotic isolates namely S. Enteritidis (75.90%), S. Paratyphi (11.90%), and S. Typhimurium (5.60%) were identified. The location of farms was significantly associated with presence of Salmonella, and the risk of infection was 10-fold higher in Nkong-ni than Santchou (pâ¯<â¯0.05). Other potential risk factors such as flock size, age of the farm (infrastructure), or water source were not associated with Salmonella infection. The prophylactic measures against avian diseases in the country must include measures against Salmonella to protect poultry industry and public health.
Assuntos
Galinhas/microbiologia , Doenças das Aves Domésticas/epidemiologia , Salmonelose Animal/epidemiologia , Salmonella enteritidis/isolamento & purificação , Salmonella paratyphi A/isolamento & purificação , Salmonella typhimurium/isolamento & purificação , Criação de Animais Domésticos , Animais , Camarões/epidemiologia , Estudos Transversais , Surtos de Doenças , Fazendas/estatística & dados numéricos , Feminino , Doenças das Aves Domésticas/microbiologia , Saúde Pública/métodos , Fatores de Risco , Salmonelose Animal/microbiologia , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Salmonella enterica serovar Paratyphi A, the causative pathogen of enteric fever, is a major public-health concern affecting millions of people around the world. We conducted whole-genome sequencing and analysis of a novel macrolide-resistant Salmonella Paratyphi A strain isolated from Karachi, Pakistan. METHODS: Genomic DNA of Salmonella Paratyphi A strain JRCGR-AK14 was sequenced on a MiSeq platform. Read quality was evaluated and paired-end reads were assembled into contigs and scaffolds. The quality of contigs and scaffolds was evaluated and assembled contigs were annotated. Virulence genes, antimicrobial resistance genes (ARGs), tRNAs, rRNAs, coding sequences and clustered regularly interspaced short palindromic repeats (CRISPRs) were identified. ARGs and mutations in quinolone-resistance determining regions (QRDRs) were identified by Antimicrobial Resistance Identification By Assembly (ARIBA) and ResFinder. Known and unknow mutations in the QRDRs were predicted. RESULTS: The genome of Salmonella Paratyphi A was calculated at 4529866 bp with 4381 genes and 1088 hypothetical proteins. Several putative genes coding for multidrug efflux pumps were identified. In addition, gene mutations conferring resistance to nitrofurantoin (e.g. marA, mdsC, Escherichia coli soxS), pulvomycin (e.g. H-NS, cpxA, E. coli EF-Tu) and fosfomycin (CRP, kdpE, E. coli glpT) were also identified. Several ARGs along with the mobile genetic element transposon Tn10 were also identified. It is evident from the results that diverse redundant mechanisms are involved in regulation of drug resistance in this strain. CONCLUSION: The current findings provide valuable data for understanding the multidrug resistance and pathogenic characteristics of clinical Salmonella Paratyphi A isolates.